Monitoring of antivitamin K-dependent anticoagulation in rodents - Towards an evolution of the methodology to detect resistance in rodents

- Prothrombin time is used to monitor anticoagulants (VKA) effect in rodents.
- Prothrombin time is associated with major drawbacks.
- Thromboelastometry is not reliable to monitor VKA effect in rats.
- Factor X activity measurement is the most sensitive and reliable monitoring method.
- Factor X is the key factor driving the prothrombin time in rats under anticoagulants.

Vitamin K antagonists are used as rodenticides for pest control management. In rodents, prothrombin time is used to monitor their effect despite its limits and the emergence of many coagulation methods. The aim of this study is to explore different coagulation monitoring methods in order to propose the best method and the best parameter to monitor vitamin K antagonists effect in rodents.The coagulation function was thus monitored with global coagulation assays and specialty assays after difethialone administration in rats.Despite many parameters obtained by thromboelastometry, only clotting time and clot formation time obtained by ExTEM were modified. Their evolution was fast with doubling time respectively of 4.0 h and 3.7 h but their increases were delayed with a lag time higher than 8 h. Conversely, prothrombin time evolution presented a lag time of only 2 h, but a higher doubling time of 7.2 h. The measurements of factor VII and X activities were the most sensitive assays to monitor vitamin K antagonists effect with almost no lag time and the fastest evolution. Nevertheless, factor X was shown to be the only key factor driving prothrombin time.Monitoring factor X activity enables to follow most effectively the anticoagulation status in rats after rodenticides administration.

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